An unexpected observation among the COVID-19 pandemic is that smokers constituted only 1.4%-18.5% of hospitalized adults, calling for an urgent investigation to determine the role of smoking in SARS-CoV-2 infection. Here, we show that cigarette smoke extract (CSE) and carcinogen benzo(a)pyrene (BaP) increase ACE2 mRNA but trigger ACE2 protein catabolism. BaP induces an aryl hydrocarbon receptor (AhR)-dependent upregulation of the ubiquitin E3 ligase Skp2 for ACE2 ubiquitination. ACE2 in lung tissues of non-smokers is higher than in smokers, consistent with the findings that tobacco carcinogens downregulate ACE2 in mice. Tobacco carcinogens inhibit SARS-CoV-2 spike protein pseudovirions infection of the cells. Given that tobacco smoke accounts for 8 million deaths including 2.1 million cancer deaths annually and Skp2 is an oncoprotein, tobacco use should not be recommended and cessation plan should be prepared for smokers in COVID-19 pandemic.
Adult ; Animals ; COVID-19 ; Epithelial Cells ; Humans ; Lung ; Mice ; Pandemics ; Peptidyl-Dipeptidase A ; SARS-CoV-2 ; Spike Glycoprotein, Coronavirus ; Ubiquitin-Protein Ligases/genetics*

Objective:To analyze the clinicopathological and immunohistochemical characteristics of the hypersensitivity pneumonia (HP) cases that were diagnosed by excisional lung biopsy, to improve the diagnosis accuracy of HP.Methods:The data of 47 HP cases diagnosed by excisional lung biopsy during the last 20 years were collected in Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, from January 2000 to June 2020. The clinicopathological features and the immunohistochemical profiles of CD3, CD4, CD8 and CD20 were analyzed using light microscopy and immunohistochemical stains.Results:The age of the patients ranged from 15 to 68 years, while the ratio of male to female was 22∶25. The main symptoms were shortness of breath and cough, and 32 cases had a history of allergen exposure. Most of the patients had restrictive impaired ventilatory function, and impaired diffusion function. The proportion of lymphocytes in bronchoalveolar lavage fluid (BALF) increased in 85.3%(29/34) of the patients, and the CD4 +/CD8 + T cell ratio was not higher than 0.8 in 31.3%(10/32) of the patients. Microscopically, 59.6%(28/47) of the cases showed nonnecrotizing granuloma/giant cells in the stroma, and 40.4% (19/47) of the cases had only giant cells. Ninety-three-point six percent of the cases(44/47) had peribronchiolar metaplasia, while 70.2%(33/47) had focal cell-rich inflammation. Forty-four cases (93.6%, 44/47) had fibrosis, which was manifested as usual interstitial pneumonia-like fibrosis (47.7%, 21 cases), nonspecific interstitial pneumonia-like fibrosis (29.5%, 13 cases), purely peribronchiolar fibrosis (6.8%, 3 cases) and mixed fibrosis (15.9%, 7 cases). Immunohistochemistry showed that CD4 + T cells were fewer than CD8 + T cells in 24 cases (55.8%, 24/43) of HP. Thirty-two HP patients had follow-up data. Among them, 7 patients had improved symptoms, 12 patients were stable, and 13 patients had worsening symptoms. Conclusions:The most common type of HP diagnosed by excisional lung biopsy is chronic HP. The clinical characteristics are long course of disease, restricted ventilation disorder and impaired diffusion function with the increase of lymphocyte proportion in BALF. Nearly 1/3 of the patients have no known history of allergen contact. The degree of fibrosis in HP patients diagnosed by excisional lung biopsy is severe, and the histologic types of fibrosis varies, but the UIP-like and/or NSIP-like fibrosis is most common. The CD4 +/CD8 + T cell ratio in lung tissues is less than 1 in more than half of the cases. Pulmonary fibrosis continued to increase in some of the patients with chronic HP, even after treatment.

Objective To summarize the characteristics of Chinese coccidioidomycosis cases, improve the diagnosis and treatment of this disease and prevent misdiagnosis as well as therapeutic error.Methods Search in databases including Medline,Wanfang,and CNKI using "Coccidioidomycosis" and "China" as index words yielded 23 articles that reported a total of 32 Chinese coccidioidomycosis cases.In addition,one patient with disseminated coccidioidomycos was treated in our center in April 2016.The demographic data,site of infection,clinical manifestations,past medical history,exposure history,imaging and laboratory findings,and pathological features of these 33 patients were analyzed.Results Among these 33 patients,7(21.2%)had visited an epidemic area and 6(18.2%)were immunocompromised.The disease involved the respiratory system,skin,bone,central nervous system,cornea,and stomach in 24,6,3,2,1,and 1 patients,respectively.Eight patients (24.2%) had multiple system involvement,and three of them died.The imaging findings included pulmonary nodules(=14),mediastinal lymphadenopathy(=5),solid shadow(=4),cavity(=4),pleural effusion(=3),multiple plaques(=2)and masses(=2).Coccidiolys cysts were detected in the affected tissues(=28)or in pus,exudate or pleural smear(=3);in addition,coccidioides mycelium and spores were found in the sputum,pus,and tissue cultures in 4 cases,among whom only 2 cases were confirmed by serological examination.The treatments included triazoles(=20),systemic or local administration of amphotericin B(=13),surgical resection of the lesion(=8),and intravenous gamma globulin(=1).Five patients died,among whom three had underlying diseases that caused immunosuppression and one was an infant.The prognoses were relatively good in the remaining patients.Conclusions Early diagnosis and proper treatment can achieve good prognosis in coccidioidomycosis patients.Multi-system involvement and immunosuppression are risk factors for poor prognosis of coccidioidomycosis.For these patients,adequate and full-course medication may prevent rapid disease progression.
China ; Coccidioides ; Coccidioidomycosis ; diagnosis ; pathology ; therapy ; Humans ; Prognosis

Objective To summarize the clinical and pathologic characteristics of patients with RosaiDorfman disease (RDD) mimicking immunoglobulin (Ig) G4-related disease (IgG4-RD).Methods Retrospectively analyze the clinical manifestations,laboratory tests,pathologic features,treatment and prognosis of RDD patients whose clinical presentations mimicked IgG4-RD in Peking Union Medical College Hospital during January 2015 to June 2017.Results Six RDD patients mimicking IgG4-RD were described,which accounted for 1.5％ of the 450 registered IgG4-RD patients.All patients were male,with the median age of 53 year and the median disease duration of 12 months.All patients had extra-nodal involvements,of which the locations included spinal cord (3/6),intracranial (2/6),skin (2/6) and liver (1/6).Increased serum IgG4 (＞1 350 mg/L) was found in 4 cases (1 360-6 410 mg/L).Seven specimens were obtained from these patients.The number of IgG4-positive plasma cells was found to be more than 50 per HPF in 3 cases,30 per HPF in 1 case.The IgG4/IgG ratio was 40％ in 2 specimens,between 10％ and 30％ in 2 specimens and 10％ in 2 specimens.All patients were treated by glucocorticoids and 4 of them were treated with combined cyclophosphamide.Five patients got partial remission by these treatments while 1 patient withdrew from further follow up.Conclusion RDD is one of the mimics of IgG4-RD.There are several differences in lab tests and pathologic features between RDD and IgG4-RD.Before the IgG4-RD is diagnosed,RDD should be excluded by specific pathologic manifestations at the first place.

Objective To analyze the clinical characteristics of IgG4-related disease (IgG4-RD)so as to improve the understanding of IgG4-RD in China.Methods IgG4-RD patients were recruited from Peking Union Medical College Hospital between January 2011 and January 2016.All patients were followedup for more than 6 months.The demographic characteristics,symptoms,organ involvements,laboratory examinations and treatment efficacy were evaluated and analyzed.Results A total of 346 patients were finally enrolled,including 230 males (66.5％) and 116 females (33.5％).The mean age of disease onset was (53.8 ± 14.2) years old.The mostly common involved organs were lymph nodes (56.4％) and submandibular glands (52.6％).Other affected organs and manifestations included:swelling of the lacrimal glands (46.5％),autoimmune pancreatitis (38.4％),pulmonary involvement (28.0％),sclerosing cholangitis (25.4％),naso-sinusitis (23.4％),parotid gland swelling (21.7％),retroperitoneal fibrosis (19.9％),large arteries involvement (9.5％),kidney involvement (obstructive nephropathy caused by retroperitoneal fibrosis was excluded) (6.9％),skin lesions (6.4％).Rare features consisted of thyroid glands,pituitary glands,gastrointestinal tract,pachymeningitis,pericardium,sclerosing mediastinitis and orchitis.The majority of patients had multi-organ involvement,such as 74.3％ patients with 3 and more,18.2％ and 7.5％ patients with 2 and single organ involvement respectively.The average IgG4-RD responder index (IgG4-RD RI) was 13.21 ±5.70.History of allergy was found in 172 (49.7％) patients.As to the laboratory tests,elevated serum IgG4 levels were confirmed in 285 (94.1％) patients,which was positively correlated with IgG4-RD RI.There were 33.5％ patients receiving monotherapy of glucocorticoid,52.6％ treated with glucocorticoids combined with immunosuppressive agents,4.9％ patients with immunosuppressant only,and 9.0％ patients with mild disease not receiving medication.The majority (336,97.1％) patients improved the above regimens.Conclusion IgG4-RD is a systemic fibro-inflammatory disease with multiple organ involvement.The mostly common involved organs include lymph node,submandibular glands,and pancreas.Glucocorticoids and immunosuppressive agents were effective for IgG4-RD.

Objective: To observe the histopathological changes and immunohistochemical expression of IgG4 in Riedle thyroiditis (RT) and to study the relationship between RT and IgG4-related diseases (IgG4-RD). Methods: A total of 5 RT patients were collected from the Department of Pathology, Peking Union Medical College Hospital during April 2012 to August 2014. The clinical and immunohistochemical features were analyzed in the 5 patients. Histopathologic analysis was performed on hematoxylin and eosin-stained sections. Results: There were one male and four female patients, aged 52 to 78 years (median 59 years). Five cases were characterized by multiple nodules of thyroid, which increased year by year. All patients were found to have surrounding tissue compression symptoms and signs. Two female patients were found to have hypothyroidism. The serum concentration of IgG was elevated in 2 cases, and the serum concentration of IgG was not tested before operation in the remaining patients. By ultrasound, all presented as low echo or medium low echo. Strong echo occasionally appeared in hypoechoic nodules. Microscopically, fibrous tissue hyperplasia was infiltrated with varying numbers of lymphocytes and plasma cells. The occlusion of phlebitis was found in 4 cases and eosinophils were found in 3 cases. IgG4 counts and IgG4/IgG ratios in 5 cases were 20/HPF, 16%; 60/HPF, 82%; 22/HPF, 28%; 400/HPF, 266% and 33/HPF, 71%, respectively. Conclusions With the similar pathological manifestations between RT and IgG4-RD, immunohistochemical staining shows that the number of IgG4 positive plasma cells and IgG4/IgG ratio of RT are increased in varying degrees. Some cases meet the diagnostic criteria of IgG4-RD, and speculate that some cases of RT belong to IgG4-RD.

OBJECTIVETo investigate the association of CD133 expression in rectal cancer tissues with neoadjuvant chemoradiotherapy (nCRT) and tumor regression grading (TRG) after nCRT.

METHODSRadical resected rectal cancer specimens and clinicopathological data of 105 patients, including 60 men and 45 women with median age of 59 years, diagnosed as locally advanced rectal cancer in Peking Union Medical College Hospital from January 2008 to December 2014 were collected retrospectively. Thirty-nine and 66 cases were histologically classified as good-moderate and poor differentiation respectively. Sixty-eight and 37 cases were clinically graded as stage I(-II( and III(-IIII( in preoperative assessment respectively. NCRT was administered in 61 cases before surgery (nCRT group). The nCRT consisted of preoperative pelvic radiotherapy using 50 Gy (2 Gy once, for 25 sessions) with FOLFOX regimen (5-fluorouracil plus oxaliplatin) for 2-3 cycles or XELOX regimen (capecitabine plus oxaliplatin) for 2 cycles. Patients underwent surgery after 6 courses of nCRT, and then received the same previous chemotherapy regimen. In nCRT group, biopsy specimens before nCRT were obtained in 45 cases. Forty-four cases received surgery alone without nCRT (surgery alone group). CD133 expression was tested by immunohistochemical Envision two-step methods. The histological TRG evaluation was performed in the nCRT group. TRG score 0-2 was defined as insensitivity to nCRT, whereas TRG score 3-4 was defined as sensitivity. CD133 expression in rectal cancer samples before and after nCRT was compared. Association of CD133 expression with TRG after nCRT was examined.

RESULTSNo significant differences of baseline parameters were found between nCRT group and surgery alone group (all P>0.05). The positive rate of CD133 in nCRT group was 70.4%(43/61,) which was significantly higher than that in surgery alone group (47.7%, 21/44)(χ(2)=5.566, P=0.018) and that in biopsy samples before nCRT group (44.4%, 20/45)(χ(2)=7.287, P=0.007). Twenty-two cases (36.1%, 22/61) in nCRT group had TRG score of 3-4 . Among these 22 cases, 11 cases were negative CD133, and constituted 61.1% (11/18) of all CD133-low expression cases in nCRT group, whereas the other 11 cases were positive CD133, and constituted 25.6%(11/43) of all CD133-high expression cases in nCRT group (χ(2)=6.974, P=0.008).

CONCLUSIONThe CD133 expression up-regulates markedly in rectal cancer after nCRT and nCRT may have potential positive modulation on CD133 expression. CD133-positive cancer reveals lower response to nCRT, suggesting CD133 may be a potential target for improving efficacy of nCRT in rectal cancer.

AC133 Antigen ; metabolism ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Chemoradiotherapy ; Deoxycytidine ; analogs & derivatives ; therapeutic use ; Female ; Fluorouracil ; analogs & derivatives ; therapeutic use ; Humans ; Leucovorin ; therapeutic use ; Male ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Staging ; Organoplatinum Compounds ; therapeutic use ; Rectal Neoplasms ; metabolism ; therapy

Objective To investigate the prevalence rate of healthcare-associated infection(HAI)in Xiangya Hospital,and provide reference for preventing and controlling HAI.Methods The cross sectional surveys on preva-lence rates of HAI,cross-sectional antimicrobial use,and bacterial detection among all hospitalized patients on the given days in 2000-2014 (except 2006)were carried out by combination of bedside investigation and medical record reviewing.Results The prevalence rates of HAI in 2000-2014 decreased from 6.30% to 3.91%,difference was statistically significant (χ2 = 35.14,P < 0.001 );prevalence rates of community-associated infection(CAI)were 15.61%-15.76%,there was no significant difference among each year.General intensive care unit (ICU)had the highest prevalence rate;respiratory tract was the most common site of both HAI and CAI;urinary catheterization rate showed a decreased tendency,arteriovenous catheterization rate showed a increased tendency,difference were both significant(χ2 = 5.21,96.24,respectively,both P <0.001).In 2008 - 2014,pathogenic detection rates for specimens from patients receiving therapeutic antimicrobial agents were 36.37%-44.51%,from patients with HAI were 34.00%-44.99%,detection rate of pathogens causing HAI were 41.57%-68.48%,all showed a increased tendency,difference was significant (χ2 = 22.78,10.03,26.49,respectively,all P < 0.001 ).Gram-negative bacteria were the main pathogens causing infection;both cross sectional and combination antimicrobial usage rates declined (P < 0.05 ).Conclusion Prevention and control of HAI,and antimicrobial management has achieved preliminary success,prevalence rate of HAI and cross sectional antimicrobial usage rate declined obviously,the main pathogen is gram-negative bacteria,and the major infection site is lower respiratory tract.

Objective To study the pathologic characteristics of eutopic endometrium in patients with endometriosis.Methods Pathologic characteristics of eutopic endometrium were studied in 176 patients with endometriosis in Peking Union Medical College Hospital from January 2007 to December 2008 retrospectively.Results About 72.2％(127/176)of eutopic endometrium were in proliferative phase,19.9％(35/176)of were observed as endometrial polyp,including 32 cases with simple endometrial polyp and 3 cases with abnormal hyperplasia combined with endometrial polyp.And 4.0％(7/176)showed abnormal hyperplasia.The incidence of pathologic changes in eutopic endometrium was 22.2％(39/176).Among 53 endometriosis patients combined with infertility,the incidence of pathologic changes of eutopic endometrium was 35.9％(19/53),which was significantly higher than 16.3％ in non-infertile patients (x2 =8.24,P =0.004).Among 65 cases with irregular menstruation,the incidence of endometrial polypus and endometrial hyperplasia were 20.0％(13/65)and 10.8％(7/65),which were significantly higher than 17.1％(19/111)and 0 in normal menstruation patients(x2 =13.839,P =0.003).Conclusions The eutopic endometrium of endometriosis were in proliferative phase state.The pathologic changes of eutopic endometrium were more in patients combined with infertility and irregular menstruation.

Objective To assess the CT characteristics of thoracoabdominal localized Castleman disease (LCD) in 55 cases and correlate with histopathologic features. Methods Fifty-five patients with LCD proved histopathologically in thorax ( n = 25 ) and abdomen ( n = 30 ) were collected during past 20 years. The unenhanced and contrast-enhanced CT were performed in all patients. Two radiologists reviewed CT images and the CT findings were analyzed simultaneously. Results In 54 patients with hyaline-vascular type ( n = 50 ) and mixed type ( n = 4 ) localized CD, the lesion typically presented as solitary mass (90. 7% , 49 cases), with irregular or lobular or infiltrative margin ( 83.3% , 45 cases),central calcification (38. 9%, 21 cases), marked enhancement (100% , 54 cases), focal non-necrosis low attenuation areas (72. 2%, 39 cases), lymphadenopathy (70.4%, 38 cases) and dilated feeding vessels adjacent to the mass (96.3%, 52 cases). One lesion with plasma cell type localized CD presented as a mass with irregular margin, mild enhancement and central necrosis. Four morphologic patterns wereclassified on CT, including solitary mass with well-circumscribed margin (n =4), irregular or lobular margin ( n = 30), infiltrative or halo-like margin ( n = 16 ), and multiple coalescent maasses ( n = 5 ). Conclusion CT features of thoracoabdominal localized CD are closely related to the location and pathological type. LCD with hyaline-vascular and mixed type has typical CT characteristics, while LCD with plasma cell type has no typical CT findings.